1. Field of the Invention
The invention concerns a surface-functionalized carrier material comprising a carrier material and at least one linker compound covalently bound to a polymeric surface of the latter, a method for the production thereof as well as a method for the solid-phase synthesis of amino acids, peptides or molecules with at least one peptide structural unit.
2. Description of Related Art
Conducting the synthesis of peptides or more complex molecules with peptide structural units in the form of so-called solid-phase syntheses is known. For this purpose, an amino acid which represents virtually the first molecular member of the peptide sequence to be produced is covalently bound to a carrier material that is not soluble in water and whose surface bears suitable functional groups. Further extension of the chain is produced by successively binding additional amino acids, which correspond to the sequence to be constructed, to the first amino acid or to the free end of the forming peptide chain. In addition to pure chain extension, the conducting of chemical modifications at the immobilized amino acid or the immobilized peptide is also known. Polystyrene is primarily used as the basic material for the solid phase (the carrier material) (refer to: F. Z. Dörwald, Organic Synthesis on Solid Phases, Wiley Publishing Co. Chemistry, Weinheim 2000, pp. 414 ff).
Two strategies are distinguished with respect to the direction of synthesis of the peptide to be produced. In the Merrifield strategy, which is also denoted as type A extension, a surface functionalization of the polystyrene is conducted by derivatizing with chloromethyl, hydroxymethyl or acrylamide groups (R. B. Merrifield, J. Am. Chem. Soc. 1963, 85, pp. 2149-2154; R. Arshady et al., J. Chem. Soc. Perkin Trans. I 1981, pp. 529-537). The covalent coupling of the first amino acid to these groups is conducted via the carboxyl group of the amino acid, i.e., the C terminal. The further construction of the chain includes a condensation of the subsequent amino acid to the amino group (the N terminal) of the already immobilized amino acid, or—in further synthesis—the immobilized peptide. According to the Merrifield strategy, synthesis is produced accordingly from the C terminal to the N terminal of the peptide. Also, in the Boc strategy derived from the Merrifield concept (R. Arshady et al., J. Chem. Soc. Perkin Trans I 1981, 529-537) or the Fmoc strategy (L. A. Carpino, G. Y. Han, J. Org. Chem. 1972, 37, 3404-3409), in which the amino group of the respective amino acids to be coupled is protected by specific protective groups, the peptide is finally bound to the solid phase via the carbonyl function of the first amino acid.
In contrast, in the inverse strategy (type B extension), chloroformic acid ester units immobilized on the surface of polystyrene are used as the starting point for the peptide synthesis (R. L. Letsinger, M. J. Kornet, J. Am. Chem. Soc. 1963, 85, 2149-2154; R. Matsueda et al., J. Am. Chem. Soc. 1975, 97, 2573-2575). The synthesis is conducted here by N-terminal coupling of the amino acids protected as tert-butyl esters in the sequence given in advance by the target sequence in the direction of the C terminal of the peptide.
It is a disadvantage in this prior art that, independent of the desired synthesis strategy, carrier materials with different functionalizations must be utilized, since the chemical properties of the respective surface function of the carrier material permit exclusively an N terminal or a C terminal coupling of the amino acid.